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(Stroke. 2006;37:2667.)
© 2006 American Heart Association, Inc.

Original Contributions

TGF-ß1 Polymorphisms and Risk of Myocardial Infarction and Stroke

The Rotterdam Study

Mark P.S. Sie, MD; André G. Uitterlinden, PhD; Michiel J. Bos, MD; Pascal P. Arp, MSc; Monique M.B Breteler, MD, PhD; Peter J. Koudstaal, MD, PhD; Huibert A.P. Pols, MD, PhD; Albert Hofman, MD, PhD; Cornelia M. van Duijn, PhD Jacqueline C.M. Witteman, PhD

From the Departments of Epidemiology and Biostatistics (M.P.S.S., A.G.U., M.J.B., M.M.B.B., H.A.P.P., A.H., C.M.v.D., J.C.M.W.), Internal Medicine (M.P.S.S., A.G.U., P.P.A., H.A.P.P.), and Neurology (M.J.B., P.J.K.), Erasmus Medical Center, Rotterdam, The Netherlands.

Correspondence to J.C.M. Witteman, PhD, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail j.witteman{at}erasmusmc.nl

Background and Purpose— Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cardiovascular and cerebrovascular complications. Transforming growth factor-ß1 (TGF-ß1) is a pleiotropic cytokine with a central role in inflammation. Little is known of the relation of variations within the gene and risk of cardiovascular and cerebrovascular disease. We therefore investigated 5 polymorphisms in the TGF-ß1 gene (–800 G/A, –509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study.

Methods— Participants (N=6456) of the Rotterdam Study were included in the current study. Analyses of the relations of genotypes with the risk of myocardial infarction and stroke were performed according to Cox proportional-hazards methods. All analyses were adjusted for age, sex, conventional cardiovascular risk factors, and medical history.

Results— We found no association with the risk of myocardial infarction. A significantly increased risk of stroke was found, associated with the T allele of the –509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to 1.48).

Conclusions— No association between the TGF-ß1 polymorphisms and myocardial infarction was observed; however, the –509 C/T and codon 10 Leu/Pro polymorphisms were associated with the risk of stroke.

Key Words: myocardial infarction • polymorphisms • stroke • transforming growth factor-ß

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